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Nat Commun. 2013;4:1438. doi: 10.1038/ncomms2445.

Ephrin-A5/EphA4 signalling controls specific afferent targeting to cochlear hair cells.

Author information

1
GIGA-Neurosciences, Developmental Neurobiology Unit, University of Liège, C.H.U. B36, Liège B-4000, Belgium.

Abstract

Hearing requires an optimal afferent innervation of sensory hair cells by spiral ganglion neurons in the cochlea. Here we report that complementary expression of ephrin-A5 in hair cells and EphA4 receptor among spiral ganglion neuron populations controls the targeting of type I and type II afferent fibres to inner and outer hair cells, respectively. In the absence of ephrin-A5 or EphA4 forward signalling, a subset of type I projections aberrantly overshoot the inner hair cell layer and invade the outer hair cell area. Lack of type I afferent synapses impairs neurotransmission from inner hair cells to the auditory nerve. By contrast, radial shift of type I projections coincides with a gain of presynaptic ribbons that could enhance the afferent signalling from outer hair cells. Ephexin-1, cofilin and myosin light chain kinase act downstream of EphA4 to induce type I spiral ganglion neuron growth cone collapse. Our findings constitute the first identification of an Eph/ephrin-mediated mutual repulsion mechanism responsible for specific sorting of auditory projections in the cochlea.

PMID:
23385583
DOI:
10.1038/ncomms2445
[Indexed for MEDLINE]

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